Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization

Nat Cell Biol. 2002 Aug;4(8):547-55. doi: 10.1038/ncb821.


beta-Arrestins are important in chemoattractant receptor-induced granule release, a process that may involve Ral-dependent regulation of the actin cytoskeleton. We have identified the Ral GDP dissociation stimulator (Ral-GDS) as a beta-arrestin-binding protein by yeast two-hybrid screening and co-immunoprecipitation from human polymorphonuclear neutrophilic leukocytes (PMNs). Under basal conditions, Ral-GDS is localized to the cytosol and remains inactive in a complex formed with beta-arrestins. In response to formyl-Met-Leu-Phe (fMLP) receptor stimulation, beta-arrestin Ral-GDS protein complexes dissociate and Ral-GDS translocates with beta-arrestin from the cytosol to the plasma membrane, resulting in the Ras-independent activation of the Ral effector pathway required for cytoskeletal rearrangement. The subsequent re-association of beta-arrestin Ral-GDS complexes is associated with the inactivation of Ral signalling. Thus, beta-arrestins regulate multiple steps in the Ral-dependent processes that result in chemoattractant-induced cytoskeletal reorganization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrestins / chemistry
  • Arrestins / metabolism*
  • Biological Transport, Active
  • COS Cells
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Macromolecular Substances
  • Models, Biological
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Rats
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / metabolism
  • Receptors, Peptide / metabolism
  • Signal Transduction
  • Two-Hybrid System Techniques
  • beta-Arrestins
  • ral GTP-Binding Proteins / chemistry
  • ral GTP-Binding Proteins / metabolism*
  • ral Guanine Nucleotide Exchange Factor / chemistry
  • ral Guanine Nucleotide Exchange Factor / metabolism*


  • Arrestins
  • Macromolecular Substances
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Peptide
  • beta-Arrestins
  • ral Guanine Nucleotide Exchange Factor
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • N-Formylmethionine Leucyl-Phenylalanine
  • ral GTP-Binding Proteins